Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

Yihang Yuan,Ming Xu,Ji Chen,Jue Wang,Peng Sun,Leilei Liang,Yunpeng Zhang

doi:10.3389/fonc.2020.00638

Yihang Yuan, Ming Xu + Show 5 more

Open Access

https://doi.org/10.3389/fonc.2020.00638

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Abstract

Colorectal cancer (CRC) is the third leading cause of death in the world. However, the key roles of most molecules in CRC remain unclear. This study aimed to identify key modules and hub genes associated with the progression of CRC. The data of the patients with CRC were obtained from the Gene Expression Omnibus (GEO) database and assessed by weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses performed in R. by WGCNA, several hub genes that regulate the mechanism of tumorigenesis in CRC were identified, which were associated with clinical traits. Next, we screened hub genes related to the progression of CRC authenticated by The Cancer Genome Atlas (TCGA) and Oncomine databases. Three hub genes (HCLS1, EVI2B, and CD48) were identified, and survival analysis was further performed. Moreover, the results of qPCR and immunohistochemistry staining revealed that HCLS1, EVI2B, and CD48 are tumor suppressor genes. Further, the functional study verified that over-expression of HCLS1, EVI2B, and CD48 can reduce the proliferation, migration, and invasion ability of CRC cells and significantly suppress CRC tumor growth in vivo. In summary, we identified three hub genes that were associated with the progression of CRC that can be applied in treatment.

Highlights

Colorectal cancer (CRC) is the most common types of gastrointestinal tumors and deadly cancer globally [1]
The results showed that these mRNAs were mainly enriched in three categories, including the biological process (BP), cellular component (CC), and molecular function (MF) categories
We confirmed the expression patterns of these three mRNAs in a colon cancer dataset from the The Cancer Genome Atlas (TCGA) database

Summary

Introduction

Colorectal cancer (CRC) is the most common types of gastrointestinal tumors and deadly cancer globally [1]. Adenomas can be surgically removed, and the prognosis is favorable in the early stages. Once cancer metastasizes to organs, the survival rates of CRC patients significantly decline [2]. It is important to explore the pathogenesis of CRC, which for developing optimal therapeutic strategies. New generation of sequencing technology has achieved breakthrough development, and an increasing number of scientists have recognized the crucial role of sequencing in life science research [3]. The high-throughput platform is considered to be the most useful instrument for analyzing tumor genes [4] and has good application prospects in the search for diagnostic and therapeutic markers for tumors [5].

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